A wide range of naphthoquinones are known in the art. Such compounds have been variously described as having antimalarial, anticoccidial and antitheilerial activity. Some compounds have also been described as possessing activity against external parasites. Thus, Fieser et al, J. Amer. Chem. Soc. 1948, 70, 3156-3165 (and references cited therein) describes a large number of 2-substituted-3-hydroxy-1,4-naphthoquinones as having antimalarial activity. A number of these compounds have also been described in U.S. Patent Specification No. 2553647 and 2553648. Further classes of 2-substituted-3-hydroxy-1,4-naphthoquinones having activity as antimalarial, anticoccidial and/or antitheilerial agents are described in U.S. Pat. Nos. 3367830, and 3347742, U.K. Patent Specification No. 1553424, and European Patent Specifications Nos. 2228, 77551, 77550 and 123,238.
European Patent No. 123,238 discloses 2-substituted-3-hydroxy-1,4-naphthoquinones which are said to be active against the human malaria parasite Plasmodium falciparum and also against Eimeria species such as E. tenella and E. acervulina, which are causative organisms of coccidiosis. 2-Substituted-3 -hydroxy-1,4-naphthoquinones(1) have been described in literature as possessing anti-protozoal activity, in particular anti-malarial. Anti-coccicidal activity has also been reported to a lesser extent. Hundreds of such compounds as possessing anti-malarial activity have been disclosed by Fieser and co-workers. All these compounds use 2-chloro-1,4-naphthoquinone (2) as one of the starting materials.

Synthesis of 2-chloro-1,4-naphthoquinone in the laboratory always resulted in a mixture of monochloro and dichloronaphthoquinone i.e. 2-Chloro and 2,3-Dichloronaphthoquinones. Material procured from market was also found to contain almost 10-12% of 2,3-dichloronaphthoquinone(3). The preparation of pure 2-chloronaphthoquinone from this material is tedious and results in loss, making it expensive. Prior art has used the condensation of trans-4-(4-chlorophenyl)cyclohexanecarboxylic acid(4) with 2-chloro-1,4-naphthoquinone(2) to give 2-chloro-3-[trans-4-(4-chlorophenyl)cyclohexyl]-1,4-naphthoquinone(5) which on hydrolysis yielded Atovaquone (6) which is a very well known antimalerial drug. We have however surprisingly found that condensation of trans-4-(4-chlorophenyl)cyclohexanecarboxylic acid (4) with the abundantly available, commercially inexpensive 2,3-dichloronaphthoquinone(3) gave an improved yield of 2-chloro-3-[trans-4-(4-chlorophenyl)cyclohexyl]-1,4-naphthoquinone(5) which on hydrolysis yielded Atovaquone(6). We report for the first time these reactions and their commercial applications which are hitherto unknown.